Project 6: Nanopatterned Surfaces for the Analysis of Tumor Cell Signaling &Migration Active migration, local invasion and dissemination of metastases are hallmark characteristics of malignant cells. These complex activities depend upon integration of information derived from soluble growth/motility factors with information gleaned from cell interactions with the extracellular matrix and with other cells. The decision network that determines the timing and directionality of tumor cell movement involves intricate signaling cascades that guide the vectorial and contractile functions of the cytoskeleton. The biochemical events of signal transduction occur in a spatially and temporally coordinated manner that then dynamically shape the cytoskeleton in specific sub-cellular regions. Thus tumor cell migration and invasion involves a precise but constantly changing subcellular nano-architecture. Until recently, understanding the signaling and cytoskeletal aspects of cellular nano-architecture was beyond the reach of cell biological investigation. Now however, the convergence of several novel nanotechnologies will permit its detailed elucidation. The first key technology involves dynamically nanopatterned surfaces that allow the display of ligands for integrins and other key cell surface receptors with control of affinity, density, and patterning that can be varied during the course of the experiment. The second technology is optically active surfaces that allow nanoscale regions of cells to be illuminated to activate fluorescence or trigger photochemical processes, but in a manner that is responsive to the interaction of the cell with the surface. The third technology uses molecular biosensors that are responsive to the state of activation of signaling proteins, thus allowing precise subcellular localization of signal transduction events. Using these approaches a team of physical scientists and cell biologists will deeply and quantitatively probe the signaling and cytoskeletal activities that control tumor cell migration.